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Opn4m2 labeling shows nuclear localization, which did not change in response to light. opn4m1, opn4m2, gr, per1b, and cry1b presented an oscillatory profile of expression in LD condition. In both DD and LD condition, dexamethasone (DEX) treatment shifted the peak expression of per1b and cry1b transcripts
GR agonists enhanced, whereas GR loss diminished, Hematopoietic stem and progenitor cell formation.
Two distinct gene clusters were found that were regulated by GRalpha: one that was regulated by GRalpha under basal conditions (presence of endogenous cortisol only), and one that was regulated upon increased activation of GRalpha.
We suggest that GR controls a gene network required for visual adaptation in the zebrafish retina and potentially integrates neuroendocrine and sensory responses to environmental changes.
This study demonistrated that disruption of GR causes a syndrome in adult zebrafish that resembles an affective disorder.
GR signaling is essential for zebrafish muscle development
The maternal gr transcript and protein participate in the maternal programming of zebrafish development.
The present study demonstrates that in zebrafish a GR isoform exists that diverges from the canonical zebrafish GR at the same position as human GRbeta from human GRalpha.
our study shows that loss of podocyte GR worsens proteinuria in settings of injury, both in vivo and in vitro.
Results indicated that the effects of childhood trauma (CT)on mood may be mediated by GRalpha translational isoforms, which then could affect negative emotional states through direct and indirect paths involving full length GRalpha and FKBP5. The animal results demonstrated that 40-kDa GRalpha could be involved in fear extinction learning by affecting BDNF mRNA expression and neuronal plasticity in a sex-dependent manner.
These findings demonstrate that specific GR translational isoforms can influence development, circadian rhythm, and inflammation through the regulation of distinct gene networks.
APPL2 overexpression could blunt the activation of glucocorticoid receptor when undergoing environmental stress.
crosstalk between GCR and PPARgamma is largely synergistic but counter-regulatory in lipogenic genes, of which enhancement prevents excessive glycerol and possibly FFA release by glucocorticoids into the circulation.
Results provide compelling evidence that glucocorticoids and GR augment but are not required for the development of functional adipose tissue in vivo.
This work provides new findings inglucocorticoid (GC) field by bringing novel understanding on how GR integrates plasma membrane, allowing GC membrane-initiated signaling that differs in presence of GnRH to disrupt GnRH-dependent signaling and luteinizing hormone secretion.
The present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes.
Absence of the GR significantly impairs fracture healing associated with a defective cartilage-to-bone transition.
Glucocorticoid receptor positively regulates transcription of FNDC5 in the liver.
this study shows that selective ablation of GR in noradrenergic neurons does not affect fundamental properties of peritoneal leukocytes
Data (including data from studies in knockout/transgenic mice) suggest that, under hypoxic conditions, muscle atrophy and elevated gene expression of ubiquitin proteasomal system-associated enzymes are mostly independent of glucocorticoid/Nr3c1 signaling.
We propose that the GC-induced mitochondrial accumulation of Bax and the interaction between the GR and Bim, Bcl-xL and Bak could play a role in the regulation of thymocyte apoptosis.
The potentiation of RANKL induced CTX release by dexamethasone was significantly less in bone marrow macrophage cells from mice with conditional knockout of the osteoclastic glucocorticoid receptor and completely absent in cells from GR(dim) mice, which carry a point mutation in one dimerizing interface of the GC receptor.
These data establish SUMO conjugation as a novel regulatory mechanism in the Hsp90 cochaperone activity of FKBP51 with a functional impact on GR signaling in a neuronal context.
These results together suggested that ERK1 phosphorylation plays a critical role in regulating GR beta expression and hydrocortisone-induce GR phosphorylation at Ser220, which is critical for the anti-apoptotic effects hydrocortisone on hepatic ischemia-reperfusion injury.
GR signaling in macrophages, playing a crucial role in tissue-repairing mechanisms, could be a potential therapeutic target during wound healing after ischemic myocardial injury
a significant protein-protein interaction between GR and CHOP, (GR-CHOP heterocomplex formation) under endoplasmic reticulum stress conditions, is reported.
This study identifies an endocrine developmental axis in which fetal GR primes the activity of PPARalpha in anticipation of the sudden shifts in postnatal nutrient source and metabolic demands.
we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined.
The guinea pig GR-specific mutations within the H1-H3 loop confer global changes within the GR-Hsp90 complex that favor FKBP51 repression over FKBP52 potentiation.
there were no differences in GCR expression in Pgp+IFN-gamma/TNF-alphahigh+CD8+ T cells between patients with bronchiolitis obliterans syndrome and stable lung transplant patients
glucocorticoid responsive element hypermethylation at exon1D of the NR3C1 gene in monozygotic twins concordant for anxious-depressive disorders suggests this region plays a role in increasing vulnerability to psychosocial stress, partly mediated by altered hippocampal connectivity.
This study examined the moderation by glucocorticoid receptor (NR3C1) gene variants of intervention effects on the developmental trajectories of alcohol abuse through adolescence. The findings highlight the importance of taking a developmental perspective on adolescent alcohol use and have implications for future intervention design and evaluation.
results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.
risk "T" rs4742170 allele disrupts binding of glucocorticoid receptor (GR) transcription factor to IL33 putative enhancer.
Single nucleotide polymorphisms in the NR3C1 gene are associated with different phenotypes in glucocorticoid receptor deficiency.
the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation was studied, and the associations between these polymorphisms and clinical outcomes was determined
Systematic review identified a number of NR3C1 CpG sites were significantly associated with trauma or psychopathology, but significant findings were often inconsistent across studies. Selected common genetic variants show no significant effect on NR3C1 CpG methylation. In contrast, there was ample evidence linking increased methylation of NR3C1 to reduced expression of this gene.
Older people with a higher NR3C1 1F exon methylation status were more likely to suffer from depression at both baseline and 2years later. Findings support the role of epigenetic factors associated with the hypothalamus-pituitary-adrenal axis in late-life depression.
SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR.
NR3C1 hypermethylation was cross-sectionally associated with high score for internalizing symptoms in in depressed and bullied adolescents
Mineralocorticoid receptor antagonism limits choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.
epigenetic changes of NR3C1-1F may provide a more in-depth understanding of the highly variable neuroendocrine and pathological sequelae of childhood trauma.
Mean NR3C1 exon 1F DNA methylation levels were significantly increased in a cohort of patients with major depressive disorder.
relaxin-GR signaling has role in hepatocellular protection against ischemia-reperfusion stress in liver transplantation
Bcl1 G/G polymorphism of glucocorticoid receptor gene is associated with bronchial asthma complicated by obesity.
topical mevastatin accelerates wound closure by promoting epithelialization via multiple mechanisms: modulation of GR ligands and induction of the long noncoding RNA Gas5, leading to c-Myc inhibition.
alpha-Viniferin (KCV) inhibits the activation of glucocorticoid receptor (GR) signaling pathway in non-androgen-dependent Prostate cancer (PCa) cells. KCV induces cancer cell apoptosis through AMP-Activated Protein Kinases-mediated activation of autophagy, and inhibits GR expression in castration-resistant prostate cancer(CRPC).
The genotypes for the NR3C1 polymorphisms in patients and controls were distributed as follows: rs6191 TT 37 : 56, GT 178 : 36, GG 332 : 609; rs6196 AA 483 : 905, AG 66 : 118, GG 2 : 4; rs10482614 GG 493 : 916, AG 61 : 108, AA 1 : 4; and rs72557310 AG 27 : 65, GG 3 : 0, AA 525 : 964. There were no significant differences in genotype frequency or in allele distributions between cases and controls.
This study reveals the role of GR in muscle fiber inhibition on intramuscular adipocytes, and identifies myostatin as a muscle-derived modulator for adipose GR level.
These results indicate that myostatin mediates maternal low protein diet-induced growth retardation, through epigenetic regulation involving FoxO3 and glucocorticoid receptor binding to its promoter.
Data indicate that higher hepatic glucocorticoid receptor (GR) expression in EHL piglets attributes mainly to the enhanced transcription of GR promoter 1-9/10 from breed-specific interaction of p53 and specificity protein 1 (Sp1).
Tissue specificities, gene expression and induction responsiveness of the porcine NR3C1 gene.
role in the breed-dependent regulation of mitochondrial genes in the liver of newborn piglets
Cloning and dna sequence analysis of the upstream flanking region of the NR3C1 gene in the domestic pig.
Effects of age, weaning and/or social isolation on the expression of genes regulating glucocorticoid response [glucocorticoid receptor).
Glucocorticoid Receptor protein expression in granulosa cells was higher in cysts from animals with spontaneous cystic ovarian disease and adrenocorticotropic hormone-induced cystic ovarian disease than in tertiary follicles from control animals.
Exposure to follicular fluid transiently increased the transcript levels of IL8 and PTGS2, and decreased the expression of SOD2, GPX3, DAB2, and NR3C1. TNF and IL6 levels were also decreased while those of NAMPT were unaffected.
Bayesian image analysis of dexamethasone and shear stress-induced glucocorticoid receptor intracellular movement
investigation of gene expression for GR, 11HSD1, and 11HSD2 in granulosa cells and theca interna layers during follicular maturation and atresia: expression of GR was largely unchanged during follicular maturation
Our results underscore a critical role for central and peripheral GR signaling in the regulation of plasma cortisol levels during stress in fish.
The E domain of the trout receptors are not involved in the nucleocytoplasmic localization of naive trout GRs, but the A/B domain, especially if linked to the corresponding trout CD region, plays a pivotal role in the cellular distribution pattern.
This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175).
, nuclear receptor subfamily 3, group C, member 1
, glucocorticoid receptor 1
, nuclear receptor subfamily 3 group C member 1
, glucocorticoid nuclear receptor variant 1
, glucocorticoid receptor alpha
, glucocorticoid receptor variant P
, glucocorticoid receptor variant beta
, glucocorticoid receptor variant gamma